1997 9 2 Carcinogenesis T eratogenesis and M utagenesis V o l 9 N o 2 1997 1 1 2 2 1 2 310015 ( ) 10ppm, B 1 (vitam in B 1) KC lo 3 ( ) N H 4 + G +, 7000 10ppm, 9, 58. 4%, ; ; ;, g, g to r g from recom binant DNA clones in m amm alian, g 5. : ; ;,, 1. C line M J. Perspectives fo r gene therapy: Inserting new genetic info rm ation into m amm alian cells by physical techniques and viral vecto rs. P harm ac T hera, 1985; 29: 69. 2. C line M J. Gene therapy: Current status and future direc2 tions. S chw eiz M ed W sch r, 1986; 116 (43) : 1459. 3. A nderson W F. P ro spects of gene therapy. S cience, 1984; 226: 401. 4. L edley FD. Som atic gene therapy fo r hum an disease: background and p ro spects. J P ed iat, 1987; Part g 110 (1) : 1, Part g 110 (1) : 167. 5. A nson D S, et al. The gene structure of hum an antihaemoph ilic facto r g. EM B O J, 1984; 3 (5) : 1053. 6. A nson D S, et al. Exp ression of active hum an clo tting fac2 cells. N ature, 1985; 315: 683. 7. Choo KH, et al. Exp ression of active hum an blood clo t2 ting facto r g in transgenic m ice: U se of a cdna w ith comp lete mrna sequence. N uc A cid R es, 1987; 15 (3) : 871. 8. Kurachi K, et al. Iso lation and characterization of a cdna coding fo r hum an facto r g. PN A S, 1982; 79 (21) : 6461. 9. E llis J, et al. Gene targeting w ith retroviral vecto rs: Re2 com bination by gene conversion into regions of nonho2 mo logous. M ol Cellu lar B iol, 1989; 9: 1621. 10. Kurata S I, et al. T he laser m ethod fo r efficient introduc2 tion of fo reign DNA into cultrued cells. E xp Cell R es, 1986; 162: 372. 11. M ann R, et al. Construction of a retrovirus pack ing m u2 tant and its use to p roduce helper- free detective retro2 virus. Cell, 1983; 33: 153. 12. Eglitis M A, et al. Retroviral vecto r fo r introduction of genes into m amm alian cells. B iotechniques, 1988; 6 (7) : 608. 13. T hom as KR, et al. H igh frequency targeting of genes to specific sites in the m amm alian genom e. Cell, 1986; 44: 419. 14. Sedivy JM, et al. Po sitive genetic selection fo r gene dis2 rup tion in m amm alian cells by homo logous recom bina2 tion. P roc N atl A cad S ci U SA, 1989; 86: 227. 83
A STUDY ON CARC INOGENESIS OF ENDOGENOUS N ITR ITE AND N ITROSAM INE, AND PREVENT ION OF CANCER H uang Yuguang et al 1, J i Judan et al 2 1 H ang z hou M un icip a l N o. g H osp ita l H ang z hou 310015, 2 D ep a rtm en t of Z hej iang F lax T ex 2 tile M ill AbstractT he cancerou s patien ts w ith salivary den sity h igher than 10ppm num ber tw ice as m any as healthy person ṡ T h is indicates that the endogenou s is co rrelated w ith the canceṙ By app lying a cu ltu red m edium m odified by vitam in B 1 o r KC lo 3. W e have found that m any bacteria in hum an body (especially the bow els) can n itrify N H 4 + to. can com b ine w ith a second am ine to n itro sam ine w h ich is a carcinogen. W e feed m ice u sing G + coccu s w h ich can lead to a p recancerou s lesion and m amm ary carcinom a, and p rove that the n itrification in viva is carcinogenesiṡ W e have tested a m ethod to p reven t the cancer a2 m ong 7000 w o rkers. T he patien ts suffered from sligh t digest o rgan sym p tom es w ith salivary den sity of over 10ppm fo r 3 con secu tive days can be ou r targets fo r p reven tive treat2 m en t u sing an tib io tics and n itro sam ine destroyerṡ T he resu lt show s that the cancer incidence rate in the con tro l group is 58. 4% h igher than that in the experim en tal group after 9 yearṡ T he difference betw een these tw o group s is statistically sign ifican t (ς 2 = 8. 51, P < 0. 01) T h is is reliab le evidence that the p reven tive treatm en t is effective w hen based on the idea that endogenou s and n itro sam ine are the cancinogenesiṡ Key wordsn itritegn itro sam ine; p reven ting cancer; incidence of cancer am inobenzyl su lfate), (NO 3 - ), (Α- naph thylam ine) NO 3 -, N 2 N H 3 (1) [ (n itrification) ] (naph thylam ino - azo - benzyl su lfate), (2) NO 3 -,, Griess, 1. : 1. 1 NO 3 - : Griess, (para - NO 3 - Griess L ieberm an 1. 2 NO 3-1: Table 1. Observa tion on ba lance of NO 3 -, in serum and ur ine object NO 3 - spesim en serum urine serum urine persons 320 22 270 22 m easured range (ppm ) 0-0. 98 0-2. 8 0-1. 23 0-1. 23 geom etric A verage (ppm ) 0. 062 0. 06 0. 168 0. 123 (3) 84
NO 3-2. 20ppm (5), 10ppm, 8ppm 3: NO 3 - (4),, NO 3 - Table 2. Estima te of in take and absorbing NO 3 -, 2 2 1 NO 3 -, NO 3-1. 3 (3) : of NO 3 - and in recipes (m g) abso rb into 2500m l of serun (ppm ) m axim al m inim al m axim al m inim al NO 3-280. 143 25. 228 112. 06 10. 09 0. 355 0. 0260 0. 142 0. 104 Table 3. m ea sured in var ious secretion s specim ens pus salivary in m iddle- ear no se sputum new bo rn babies healthy fasting 2-10 days cancer discharge secretion w ith in 2 days persons after operation cases persons 123 23 100 100 94 12586 42 392 m easured range of (ppm ) 0-80 0-20 0-40 0-20 0-0. 1 0-80 0-80 0-80 > 10ppm in 36 2 5 4 0 1198 4 80 cases > 10ppm % 29. 3 8. 7 5 4 0 10. 5 9. 5 20. 4 1 3, N H 3 N H 4 +, 10ppm,, (endogenou s 0. 1ppm, 86. 6%, > 10ppm 1. 5 (3) :, 210 1520ppm G + 9. 5%,, 1g2 NO 3 -,, 1,, 10ppm 1. 4 (6) : 3, > 10ppm, KC lo 3 o r vitam in B 1,, 1. 6 (7) : N H 4 + 530ppm, (n itrification) and n itro sam ine),, NO 2 - > O 2, O 2, 10ppm 4 85
,, 5, Table 4. The results of carc inogenesis with endogenous and n itrosam ine in m iceṡ series feeding num ber p recancerius lesion breast cancer e x (A ) G + coccus 27 2 (7. 4) 1 (3. 7) g p e ro r u im (B) G + coccus+ am inopyrine 33 1 (3. 0) 1 (3. 0) p s e n ta (C)A spergillus niger 40 3 (7. 5) 3 (7. 5) l contro l group (D )only rice and w ater 24 0 0 Table 5. Sym ptom s of endogenous com par ison with sym ptom s of habitua l con stipa tion 45 cases of endogenous 45 cases of habitual constipation symp tom s cases percentage % cases percentage % D istention in abdom en 29 64 Fart 15 33 Constipation 15 33 45 100 Loo sing appetite 18 40 M outh odo r bitter teste 11 24 14 31 W eak 16 36 D izzy giddy 12 27 20 44 D igestive o rgan inflamm ation 2 4. 4 NO 2> 10ppm per 3 days 45 100 0 0 6 7: Table 6. Cancer position d istr ibution s in the (7) : 1952, 6000,,,,, 2. 2. 1 : 19601977 18 112, 124g10, ( 19741976 102. 43g10, 83. 25g10 ) 2. 2, 6: Stom ach f lax textile m ill (1962-1976) cancer po sition cases percent 2. 3 2. 4, 27 24. 1 L iver 15 13. 4 O esophagus 4 3. 6 Bow els 10 8. 9 Rhinopharynx 10 8. 9 L ung 9 8. 0 Cervix uteri 6 5. 4 B reast 8 7. 1 U rinary tract 4 3. 6 L eukem ia 6 5. 4 O thers 13 11. 6 To tal cases 112 100. 0 86
Table 7. Sm ok ing and dr ink ing habit correla tion with cancer in f lax textile m ill (survey in 40-60 years old of workers dur ing 1974-1983) Item Smoking cigarette p iece. daily capacity no > 10 10-20 > 20 to tal over 20 years no drinking w ine ounce. daily smoking+ drinking som e- over tim es < 5 5-10 > 10 To tal a few 20 yes no years persons 311 78 110 124 312 107 364 64 117 63 33 277 33 197 195 cancer cases 7 1 11 12 24 12 14 3 6 4 4 17 3 14 4 % 2. 3 1. 3 10 9. 7 7. 7 11. 2 4. 0 4. 7 5. 1 6. 3 12. 1 6. 1 9. 1 7. 1 2. 6 :, 2. 5 :, 8: Table 8. A ir pollution by bacter ia carr ing in f lax dust correla tion w ith cancer ( 1960. 1-1977. 12) Item num ber of bacteia in air (diam eter 9cm of culture p late expo se 5 m inute) 900-1440 15-32 Series cleaning adm inistration+ To tal row flax w arpw eft w eaving p lant room sp inning pow er dinning dusty+ T atal m aterial softining o thers o thers persons 64 111 150 230 555 4342 670 180 5192 136 Cancer cases 8 4 5 6 23 79 7 3 89 7 incidence (10) 218 (a) 90 (b) 270 (c) (a): (b) ς 2 = 20. 58P < 0. 01 (a): (c) ς 2 = 0. 46P > 0. 05 3. : 3. 1 : 1977, 2. 6 : 14, 6, 2030,,,,,, NO 2-10 40ppm, 9 > 10ppm 30 ( 8 ),,, 4,, 56. 2% 0. 5-10ppm 1437, > 20ppm 15. 6%,,,, 2635, 3512 3. 2 :, 87
,, NO 3 -,,,, 3. 3 9:, Table 9. Sta tistics of effect of preven ting cancer in f lax textile m ill. Group Experim ental group Contro l group Term mo rbidity mo rtality mo rbidity Period (year) 1962-76 77-85 86-88 1977-88 1989 1990 1962-76 77-85 P reventive p ractice no yes yes yes no no no no N um ber of persons 2635 3517 4246 3714 3773 2484 3512 3875 Cancer cases 54 (a) 60 (c) 18 78 12 21 58 (b) 105 (d) Incidence rate (1g10) 137 190 141 175 318 845 110 301 Standardize (1g10) N ga 92 N ga N ga N ga N ga N ga 98 (c) : (b) ς 2 = 1. 33 P > 0. 05 (c) : (d) ς 2 = 8. 51P < 0. 01 : 1. 19771985, 58. 4%, 2. 19771985 53g10 5, 191g10 5, 3. 6,, 3., 19891990 19771988 1. 84. 8, 4. 1986, 19861988, 5. 1986, 3. 4, 1, F igu re 1. Com parison of cancer incidence rate betw een the experim en t group and the con tro l group in flax tex tile m ill. 1977, 1., 1952 2030, 1977 4550,, 4550 4045 2. 5 1977 88
2., 3. 4. 3. 5 58. 4%, 17, 3.,, 3. 6,,,,,,,,, 4.,, 1. 1520,,,,, (U ICC ), (8), 510, 1cm, 150300 129210, U ICC, 2. 58. 4%?, (supp l) : 2446., 9, 197785 25. 1%, 27. 9%1986 197785 20. 7%, 25. 8%, 25% 4560 16. 6%, 5, 4 2,, 1973: 40. 16. 9%,,,, (,,,! ) 1.... :, 1981: 575. 2. L ijinsky W. N itro sam ines and nitro sam idies in the etio lo2 gy of stom ach bow el cancers. Cancer R es, 1977; 40 3..., 1983: 5 (1) : 6. 4. W agner DA. Young V R. Tannenbaum SR, M amm alian nitrate bio synthesis: incopo ration of N H 3 into nitrate is enhanced by endo toxin treatm ent,m edical seiences. P roc N atl A cad S ci U SA, 1983; 80 (7) : 4518 5..., 1973: 20, 201. 6..., 1962: 135. 7..., 1986: 10. 8.,.. 89